Oxidative Stress, Inflammatory Mediators, and Dementia: An Integrative Review
DOI:
https://doi.org/10.47134/ijatm.v3i1.107Keywords:
Oxidative Stress, Inflammation, Dementia, Alzheimer’s Disease, NeurodegenerationAbstract
This study aims to provide an integrative understanding of the complex relationship between oxidative stress, inflammatory mediators, and dementia, particularly Alzheimer’s disease. Employing a qualitative descriptive design through a library-based study, this research systematically analyzes recent peer-reviewed literature from 2015 to 2025. Data were collected through comprehensive literature tracing and document analysis of academic articles, theoretical reviews, and clinical findings related to oxidative and inflammatory mechanisms in neurodegeneration. The data were processed through stages of thematic identification, reduction, categorization, and inductive interpretation to derive a holistic understanding of the phenomenon. The results reveal that oxidative stress and neuroinflammation act as interdependent and self-reinforcing mechanisms in the pathogenesis of dementia. Mitochondrial dysfunction, excess reactive oxygen species (ROS), and chronic activation of inflammatory pathways—particularly NLRP3 and NF-κB—were identified as core contributors to neuronal degeneration and cognitive decline. Furthermore, evidence highlights the critical role of systemic inflammation in amplifying central nervous system damage through blood–brain barrier disruption. These findings emphasize the need for multi-targeted therapeutic approaches integrating antioxidant and anti-inflammatory strategies, rather than isolated single-pathway treatments. The study contributes to the advancement of theoretical frameworks linking oxidative and inflammatory pathways in neurodegeneration and underscores their relevance for preventive and therapeutic innovation. In conclusion, this integrative review enriches the understanding of dementia as a multi-system disorder, providing conceptual and practical insights for future translational research in neurodegenerative disease management.
References
Abraham, D., P. P. (2024). A methodological framework for descriptive phenomenological research. Western Journal of Nursing Research, 47, 125–134. https://doi.org/10.1177/01939459241308071
Ahmad, S., Yang, W., Orellana, A., Frölich, L., De Rojas, I., Cano, A., Boada, M., Hernández, I., Hausner, L., Harms, A., Bakker, M., Cabrera-Socorro, A., Amin, N., Ramirez, A., Ruiz, A., Van Duijn, C., & Hankemeier, T. (2024). Association of oxidative stress and inflammatory metabolites with Alzheimer’s disease cerebrospinal fluid biomarkers in mild cognitive impairment. Alzheimer’s Research & Therapy, 16. https://doi.org/10.1186/s13195-024-01542-4
Altahrawi, A., James, A., & Shah, Z. (2025). The role of oxidative stress and inflammation in the pathogenesis and treatment of vascular dementia. Cells, 14. https://doi.org/10.3390/cells14080609
Bai, R., Guo, J., Ye, X., Xie, Y., & Xie, T. (2022). Oxidative stress: The core pathogenesis and mechanism of Alzheimer’s disease. Ageing Research Reviews, 77. https://doi.org/10.1016/j.arr.2022.101619
Bandaranayake, P. (2024). Application of grounded theory methodology in library and information science research: An overview. Sri Lanka Library Review. https://doi.org/10.4038/sllr.v38i2.70
Belotto, M. (2018). Data analysis methods for qualitative research: Managing the challenges of coding, interrater reliability, and thematic analysis. The Qualitative Report. https://doi.org/10.46743/2160-3715/2018.3492
Bhatia, V., & Sharma, S. (2020). Role of mitochondrial dysfunction, oxidative stress and autophagy in progression of Alzheimer’s disease. Journal of the Neurological Sciences, 421. https://doi.org/10.1016/j.jns.2020.117253
Bingham, A. (2023). From data management to actionable findings: A five-phase process of qualitative data analysis. International Journal of Qualitative Methods, 22. https://doi.org/10.1177/16094069231183620
Birla, H., Minocha, T., Kumar, G., Misra, A., & Singh, S. (2020). Role of oxidative stress and metal toxicity in the progression of Alzheimer’s disease. Current Neuropharmacology, 18, 552–562. https://doi.org/10.2174/1570159x18666200122122512
De Oliveira, J., Kucharska, E., Garcez, M., Rodrigues, M., Quevedo, J., Moreno-Gonzalez, I., & Budni, J. (2021). Inflammatory cascade in Alzheimer’s disease pathogenesis: A review of experimental findings. Cells, 10. https://doi.org/10.3390/cells10102581
Dhapola, R., Hota, S., Sarma, P., Bhattacharyya, A., Medhi, B., & Reddy, D. (2021). Recent advances in molecular pathways and therapeutic implications targeting neuroinflammation for Alzheimer’s disease. Inflammopharmacology, 29, 1669–1681. https://doi.org/10.1007/s10787-021-00889-6
Doyle, L., McCabe, C., Keogh, B., Brady, A., & McCann, M. (2019). An overview of the qualitative descriptive design within nursing research. Journal of Research in Nursing, 25, 443–455. https://doi.org/10.1177/1744987119880234
Fanlo-Ucar, H., Picón-Pagès, P., Herrera-Fernández, V., Ill-Raga, G., & Muñoz, F. (2024). The dual role of amyloid beta-peptide in oxidative stress and inflammation: Unveiling their connections in Alzheimer’s disease etiopathology. Antioxidants, 13. https://doi.org/10.3390/antiox13101208
Fife, S., G., J. (2024). Deductive qualitative analysis: Evaluating, expanding, and refining theory. International Journal of Qualitative Methods, 23. https://doi.org/10.1177/16094069241244856
Güler, E. (2025). Comparative analysis of oxidative stress, inflammatory markers, and neurotrophic factors in healthy controls, vascular dementia, and Alzheimer’s dementia. Haydarpasa Numune Training and Research Hospital Medical Journal. https://doi.org/10.14744/hnhj.2025.93276
Hsu, Y., Huang, Y., Tsai, S., Kuo, Y., Lin, J., Ho, H., Chen, J., Hsia, K., & Sun, Y. (2023). Efficacy of probiotic supplements on brain-derived neurotrophic factor, inflammatory biomarkers, oxidative stress, and cognitive function in patients with Alzheimer’s dementia: A 12-week randomized, double-blind active-controlled study. Nutrients, 16. https://doi.org/10.3390/nu16010016
Jimenez, S., B.-M., J., & De La Torre, R. (2024). How do university libraries contribute to the research process? The Journal of Academic Librarianship. https://doi.org/10.1016/j.acalib.2024.102930
Kalpokaite, N., & Radivojevic, I. (2018). Demystifying qualitative data analysis for novice qualitative researchers. The Qualitative Report. https://doi.org/10.46743/2160-3715/2019.4120
Leng, F., & Edison, P. (2020). Neuroinflammation and microglial activation in Alzheimer disease: Where do we go from here? Nature Reviews Neurology, 17, 157–172. https://doi.org/10.1038/s41582-020-00435-y
Lopez-Rodriguez, A., Hennessy, E., Murray, C., Nazmi, A., Delaney, H., Healy, D., Fagan, S., Rooney, M., Stewart, E., Lewis, A., Barra, N., Scarry, P., Riggs-Miller, L., Boche, D., Cunningham, M., & Cunningham, C. (2021). Acute systemic inflammation exacerbates neuroinflammation in Alzheimer’s disease. Alzheimer’s & Dementia, 17, 1735–1755. https://doi.org/10.1002/alz.12341
Novoa, C., Salazar, P., Cisternas, P., Gherardelli, C., Vera-Salazar, R., Zolezzi, J., & Inestrosa, N. (2022). Inflammation context in Alzheimer’s disease, a relationship intricate to define. Biological Research, 55. https://doi.org/10.1186/s40659-022-00404-3
Pappolla, M., Martins, R., Poeggeler, B., Omar, R., & Perry, G. (2024). Oxidative stress in Alzheimer’s disease: The shortcomings of antioxidant therapies. Journal of Alzheimer’s Disease, 101, S155–S178. https://doi.org/10.3233/jad-240659
Perluigi, M., Di Domenico, F., & Butterfield, D. (2024). Oxidative damage in neurodegeneration: Roles in the pathogenesis and progression of Alzheimer disease. Physiological Reviews, 104(1), 103–197. https://doi.org/10.1152/physrev.00030.2022
Plascencia-Villa, G., & Perry, G. (2023). Roles of oxidative stress in synaptic dysfunction and neuronal cell death in Alzheimer’s disease. Antioxidants, 12. https://doi.org/10.3390/antiox12081628
Pratt, M. (2025). On the evolution of qualitative methods in organizational research. Annual Review of Organizational Psychology and Organizational Behavior. https://doi.org/10.1146/annurev-orgpsych-111722-032953
Rummel, N., & Butterfield, D. (2021). Altered metabolism in Alzheimer disease brain: Role of oxidative stress. Antioxidants & Redox Signaling, 35, 987–1005. https://doi.org/10.1089/ars.2021.0177
Scarian, E., Viola, C., Dragoni, F., Di Gerlando, R., Rizzo, B., Diamanti, L., Gagliardi, S., Bordoni, M., & Pansarasa, O. (2024). New insights into oxidative stress and inflammatory response in neurodegenerative diseases. International Journal of Molecular Sciences, 25. https://doi.org/10.3390/ijms25052698
Tadokoro, K., Ohta, Y., Inufusa, H., Loon, A., & Abe, K. (2020). Prevention of cognitive decline in Alzheimer’s disease by novel antioxidative supplements. International Journal of Molecular Sciences, 21. https://doi.org/10.3390/ijms21061974
Tamagno, E., Guglielmotto, M., Vasciaveo, V., & Tabaton, M. (2021). Oxidative stress and beta amyloid in Alzheimer’s disease: Which comes first? Antioxidants, 10. https://doi.org/10.3390/antiox10091479
Thakur, S., Dhapola, R., Sarma, P., Medhi, B., & Reddy, D. (2022). Neuroinflammation in Alzheimer’s disease: Current progress in molecular signaling and therapeutics. Inflammation, 46, 1–17. https://doi.org/10.1007/s10753-022-01721-1
Togia, A., M., A. (2017). Research methods in library and information science. https://doi.org/10.5772/intechopen.68749
Twarowski, B., & Herbet, M. (2023). Inflammatory processes in Alzheimer’s disease—Pathomechanism, diagnosis and treatment: A review. International Journal of Molecular Sciences, 24. https://doi.org/10.3390/ijms24076518
Vila-Henninger, L., D., C., Van Ingelgom, V., Caprioli, M., Teuber, F., Pennetreau, D., Bussi, M., & Gall, C. (2022). Abductive coding: Theory building and qualitative (re)analysis. Sociological Methods & Research, 53, 968–1001. https://doi.org/10.1177/00491241211067508
Vogrinc, D., Kramberger, G., Emeršič, A., Čučnik, S., Goričar, K., & Dolžan, V. (2023). Genetic polymorphisms in oxidative stress and inflammatory pathways as potential biomarkers in Alzheimer’s disease and dementia. Antioxidants, 12. https://doi.org/10.3390/antiox12020316
Walker, K., Page, L., Terrando, N., Duggan, M., Heneka, M., & Bettcher, B. (2023). The role of peripheral inflammatory insults in Alzheimer’s disease: A review and research roadmap. Molecular Neurodegeneration, 18. https://doi.org/10.1186/s13024-023-00627-2
Xie, J., Van Hoecke, L., & Vandenbroucke, R. (2022). The impact of systemic inflammation on Alzheimer’s disease pathology. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.796867
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Komang Trisna Sumadewi, Saktivi Harkitasari, Fransiscus Fiano Anthony Kerans
This work is licensed under a Creative Commons Attribution 4.0 International License.
